miR-34a has been identified as a tumor suppressor in several tumors, but its involvement in gallbladder cancer (GBC) has not been reported. In this study, the miR-34a level and telomere length were measured in 77 gallbladder adenocarcinomas and 36 peritumoral tissues by real-time PCR. Forced miR-34a expression was established by an adenovirus carrying a miR-34a expression cassette. The colony-forming ability of isolated CD44+CD133+ GBC tumor stem-like cells was measured by matrigel colony assay. The xenograft tumor models were established by inoculating nude mice with CD44+CD133+cells. Results showed that significantly lower miR-34a expression and longer telomere length were observed in gallbladder adenocarcinoma tissues, which correlated with poor prognosis of GBC patients. Forced overexpression of miR-34a inhibited the colony-forming ability of CD44+CD133+ GBC tumor stem-like cells in vitro and xenograft tumor growth in vivo. Injection of Ad-miR-34a downregulated PNUTS expression and reduced telomere length in xenograft GBC tumor cells. In conclusion, miR-34a is a tumor suppressor in gallbladder cancer. Both low miR-34a expression and long telomere length are markers for poor prognosis of patients with gallbladder adenocarcinoma. Our study also suggests that the miR-34a gene could be a target for targeting therapy of GBC.
p38 MAPK (mitogen-activated protein kinase) is a critical regulator in lung inflammation. It can be inactivated by DUSP1 (dual-specificity phosphatase 1) which was identified as a putative target of miR-429. miR-429 mimics directly targeted to the 3'-UTR of the gene encoding DUSP1 may result in the translational attenuation of DUSP1. Moreover, the phosphorylation of p38 MAPK was prolonged after miR-429 mimic treatment. Additionally, miR-429 expression was sensitive to LPS (lipopolysaccharide) stimulation and the miR-429 mimics increased the production of pro-inflammatory cytokines. However, anti-miR-429 reduced the LPS-induced production of pro-inflammatory cytokines. These results provide direct evidence that miR-429 is involved in the LPS-induced inflammatory response. In parallel with miR-429, miR-200b and miR-200c, but not miR-200a or miR-141, shared similar effects. In vivo, LPS induced the expression of miR-429, miR-200b and miR-200c in lung. At the same time, inhibiting these miRNAs by anti-miRNAs attenuated the LPS-induced pulmonary inflammatory response and injury. These findings reveal that miR-429 possesses pro-inflammatory activities and may be a potential therapy target for LPS-induced lung injury.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.